The worlds biggest listed pure-play stem cell developer has a busy slate of clinical work, notably in therapies for advanced heart failure, chronic back pain and graft-versus-host disease (GvHD).
Now these programs are approaching a thrilling denouement and, as the Demtel man enthused, theres more: Mesoblast (ASX:MSB) is also undertaking an expanded coronavirus trial after a 12-patient effort showed promising results in treating acute respiratory distress syndrome (Ards), the usual cause of death with COVID-19.
The patients received infusions of Mesoblasts allogeneic (off the shelf) mesenchymal stem cell candidate, remestemcel-L, acquired from Osiris for $106m in 2013.
Meanwhile, results from two phase III trials are expected this (September) quarter: a 566-patient effort for chronic heart failure and a 404-patient trial for chronic lower back pain caused by disc degeneration.
And in September, the US Food and Drug Administration will rule on whether or not the company can market its GvHD therapy on American shores.
Mesoblast founder and CEO Prof Silviu Itescu notes that across all its therapies the company is targeting the most severe cases where alternative therapies dont exist.
Mesoblasts proprietary process selects precursor and stem cells from the bone marrow of healthy adults, creating a master cell bank. This cell kitty is then expanded into thousands of doses for off-the-shelf use, without the need for tissue matching.
Mesoblast is targeting a common market across all its disease indications: inflammation. In the case of heart disease, tissue macrophages (cells) churn out inflammatory factors that damage heart muscle and cause fibrosis and vascular dysfunction.
The stem cells respond to severe inflammation by switching the culprit macrophages off and converting them to nice cells that actually protect the heart muscle.
This is the central mechanism in each of our disease states: heart failure, back pain, GvHD and rheumatoid arthritis, Professor Itescu says. We have the potential to make a big difference in some very big disease states where inflammation is central.
Backed by the Pratt familys listed investment vehicle Thorney Investments, Mesoblast debuted on the ASX in 2004 and reached a peak valuation of $2.5bn in 2011 before suffering a reality check.
Culprits included a phase II heart trial that failed to meet primary endpoints, a badly executed Nasdaq listing and Israel pharma house Teva Pharmaceuticals decision to walk away from a heart program partnership in 2016.
Mesoblast dual listed on the Nasdaq in November 2015, accompanied by a $US63m capital raising.
The companys Ards and GvHD programs are based on mesenchymal stem cell assets acquired from US pharma group Osiris Therapeutics in October 2013.
Mesoblasts own-developed cells are called mesenchymal precursor cells and they are being developed for rheumatoid arthritis and diabetic nephropathy, as well as the aforementioned heart failure and lower back pain programs.
Ards is bought on by an excessive immune response to the virus in the lungs. The immune cells produce inflammatory cytokines, which destroy lung tissue and can also damage the liver, kidney and heart.
Remestemcell-L has the potential to tame the cytokine storm in Ards and may offer a life-saving treatment for those unfortunate individual sufferers of COVID-19 Ards, Professor Itescu says.
Mesoblasts COVID-19 proclamations have been coming so thick and fast that its been Ard(s) just to keep up. But the core excitement cluster was around Mesoblasts April 23 disclosure of the results of the trial at New Yorks Mt Sinai Hospital, covering moderate to acute Ards cases.
Under the compassionate use protocol, the patients were treated with two infusions of remestemcel-L over the first five days.
The results? Nine of the 12 patients came off a ventilator within a median 10 days, with 83 per cent survival (the Grim Reapers spin on this is that two of them died).
In comparison, only 9 per cent of patients at one reference hospital (38 out of 445 patients) were able to come off the ventilator with standard-of-care treatment.
Another US hospital reported that only 38 patients of 320 or 12 per cent survived.
Of course, 12 people good and true are adequate numbers for a jury, but sub-optimal to comprise a statistically significant trial.
Thus, the company is enrolling 300 patients in a phase III, randomised, controlled trial of severe Ards patients at 30 sites.
The first patients were dosed in early May, with about 15 sites established as the company chases the disease from the northeast to the southern states.
Mesoblast chief medical officer Professor Fred Grossman says the company is carefully choosing hot spots such as Alabama which, as of late May had the no vacancy signs outside its intensive care wards.
The sites are recruiting quite quickly, he says. There is a tremendous interest in this study.
The trial leaders will undertake an interim analysis at 30 days, and when 30 per cent of patients have reached their primary endpoint. At that point the trial can be dumped on futility grounds, or expanded to the control group because it appears to be working.
Remestemcell-L has investigational new drug (IND) status with the US Food and Drug Administration, meaning the company swiftly can initiate trials on patients with very dismal prospects.
Long-suffering Mesoblast investors will recall that the companys shares tumbled 28 per cent in November 2018 after a 159-patient trial of Rexlemestrocel-L (Revascor) for end-stage heart failure did not meet its primary endpoint of weaning patients from left ventricle assist devices (LVADs or heart pumps).
The company claimed the endpoint was set by the independent !!! investigators and was of little real clinical interest. What really mattered was that the trial showed reduced gastrointestinal bleeding by 76 per cent and hospitalisations by 65 per cent.
Investors are now nervously awaiting the first readout of the broader 566-patient chronic heart failure trial across 59 US sites.
Mesoblast targeted patients with class three or four disease, the sickest 15 to 20 per cent of patients who have failed standard-of-care drugs.
Class three patients have a 20 per cent chance of dying within two years while with class four its a case of flip a coin that you will be around in 12 months.
At this stage, Mesoblast retains its heart treatment rights except in China, where it is partnered with Tasly Pharmaceutical.
Mesoblasts phase III back pain trial aimed to enroll 404 patients with lower back pain caused by degenerative disc disease.
The endpoint of the trial, dubbed MPC-06-ID, is an improvement in pain and function over 24 months.
As with the heart trial, results are imminent and its a toss-up as to what release will hit the ASX announcements feed first.
The company is liaising with its global back pain partner Grunenthal GmbH about the clinical protocol for a European phase III confirmatory trial.
In Japan, Mesoblast is partnered with JCR Pharmaceutical for its approved GvHD treatment called Temcell and its off and racing in that smallish but enthusiastic market.
Meanwhile, the company is angling to enter the US market for a similar GvHD treatment, branded Ryoncil.
GvHD afflicts about half of the 30,000 patients annually undergoing allogeneic bone marrow transplant, typically for blood cancers, with their bodies rejecting the alien transplant.
In March, the FDA granted priority review with a September 30 action date, but we might have a good idea of the outcome in August.
Why? Because thats when the FDAs relevant advisory committee meets to vote on the matter and the (virtual) gathering is open to the public.
A date is yet to be set. While advisory committee views are not binding on the FDA, they usually presage the final decision.
If approved, Mesoblast could be selling Ryoncil in the US by the time were carving the Christmas turkey (badly, in the case of your columnist).
Buoyed by the COVID-19 results, Mesoblast in May wasted no time tapping institutional investors for an idle $US90m ($129.6m) in a placement.
Mesoblast already had a healthy cash balance of $US60m.
The raising was struck at $3.20 a share, a modest 7 per cent discount to the prevailing price.
The funds, in the main, will be used to scale-up manufacturing of remestemcell-L and to support the phase III trial, as well as for working capital and general corporate purposes.
The company also has $US67m available through existing financing facilities and partnerships.
Mesoblast reported revenue of $US31.45m for the nine months to March 2020, up 113 per cent. The reported loss narrowed 34 per cent to $US45.3m, reflecting curtailed research and development spend by $US7.5m, or 15 per cent.
The revenue included $US5.9m of JCR royalties from Temcell sales in Japan and milestone revenue of $US25m.
The company stands to pocket up to $US150m of royalties and milestones from Grunenthal prior to any European launch of Revascor.
Successful sales could result in up to $US1bn in milestone payments.
Over the last decade, Mesoblasts ASX shares have traded as high as $9 (October 2011) and as low as $1.03 (December last year).
To the Meso-sceptics the company has promised far too much with limited commercial success, while raising $1bn since listing 16 years ago.
Dare we say that Mesoblast now looks more focused and to be getting somewhere?
When we last covered Mesoblast in March 2019, Professor Itescu said he was 95 per cent certain the company would do what no other Aussie biotech in phase III had done: win FDA drug approval.
Well, Clinuvel has stolen that Aussie first honour, but Mesoblast is well placed to get over the line with a GvHD treatment in the US, which presents a market eight times the size of Japans.
Its certainly rare for a biotech to expect results for three major trials and a key regulatory decision in the space of months.
If the heart and back pain results are definitively positive and the FDA green lights GvHD, the company hits the jackpot. If two or more of them bomb lets not go there.
Your ultra conservative columnist regards the COVID-19 stuff as the icing on the cake with an outside chance of success, especially given the hundreds of other programs in the coronavirus-busting sector.
Disclosure: Dr Boreham is not a qualified medical practitioner and does not possess a doctorate of any sort. But he hopes to become proficient in turkey carving by December 25.
This column first appeared in Biotech Daily.
Get the latest Stock & Small Caps news and insights direct to your inbox.
It's free. Unsubscribe whenever your want.
You might be interested in
See the original post here:
Dr Borehams Crucible: Mesoblast within months of 3 major trial results, key regulatory decision - Stockhead
- Woman Who Conceived Twins in Rape Rejects Abortion, Shares How Her 21-Year-Old Twins Saved Her Life - The Epoch Times - October 13th, 2022
- Kid Captain Eli Belser takes the field with Hawkeyes, celebrating two years cancer free - UI The Daily Iowan - September 8th, 2022
- How space technology like the James Webb telescope is improving healthcare on Earth - The National - July 27th, 2022
- How COVID-19, Long COVID, and COVID Vaccines Differ Between Males and Females - CreakyJoints - July 27th, 2022
- Researchers find fabrication of artificial heart for transplant - ThePrint - July 19th, 2022
- Paolo Macchiarini - Wikipedia - July 3rd, 2022
- President Freeman Hrabowski prepares for retirement after turning UMBC into the top producer of Black M.D., Ph.D. graduates - Afro American - July 3rd, 2022
- Women find community in STEM fields at UA - The University of Alabama Crimson White - April 19th, 2022
- Poker Run event planned to benefit twins with rare syndrome - The Andalusia Star-News - Andalusia Star-News - April 6th, 2022
- Alabama Stem Cells | Stem Cell TV - September 12th, 2019
- Only Cosmetic Stem Cell Therapy in Alabama - msbmd.com - April 20th, 2019
- Stem Cell Therapy in Houston, TX | National Stem Cell Centers - March 23rd, 2019
- Central Alabama Pain Management Center Established 1993 - March 6th, 2019
- Stem Cell Mobile Alabama 36607 - January 4th, 2019
- Stem Cell Birmingham Alabama 35282 - August 30th, 2018
- USA College of Medicine - University of South Alabama ... - July 24th, 2018
- Researchers find new glioblastoma inhibitor - Patient Daily - August 24th, 2017
- A Chip That Reprograms Cells Helps Healing, At Least In Mice - Alabama Public Radio - August 12th, 2017
- 'Happiness' Explores The Complex Push And Pull Of Human Relationships - Alabama Public Radio - August 12th, 2017
- Hampton Creek to enter clean meat market in 2018: 'We are building a multi-species, multi-product platform' - FoodNavigator-USA.com - June 30th, 2017
- Brain Tumors: Still Devastating, but Treatment Has Come a Long Way - Newswise (press release) - June 20th, 2017
- Walk for "terrible, awful" disease - Timmins Press - June 18th, 2017
- Rare disease hits 2 of family's 4 children - The Ledger - June 18th, 2017
- Hill-Rom Holdings, Inc. (HRC) Reaches $76.89 52-Week High, Biotime (NYSEMKT:BTX) Shorts Increased By 4.64% - UtahHerald.com - June 13th, 2017
- STEM College Students Who Learn by Example May Lack Key Attribute - GoodCall News (blog) - June 13th, 2017
- Wolf Evolution and Settled Science - PLoS Blogs (blog) - June 8th, 2017
- 3D-Printed Patch Mends Hearts - Photonics.com - June 6th, 2017
- When states have strong guns laws, they also have fewer fatal police shootings - Los Angeles Times - May 19th, 2017
- Top graduating senior in 'crazy race to the finish line' | Berkeley News - UC Berkeley - May 9th, 2017
- 3D-printed patch could lead to new treatments for patients after a heart attack - Biotechin.Asia - May 5th, 2017
- Meet Curry Cates: 2017 Big Man on Campus - The Auburn Plainsman - April 28th, 2017
- Andrews Institute Looks Ahead - Inweekly - April 27th, 2017
- UMN research team fixes broken hearts with 3D-printed tissue patch - Minnesota Daily - April 27th, 2017
- Bengals set to hold onto McCarron for at least 1 more year | Sports ... - Newsexaminer - April 27th, 2017
- Andrews Institute Celebrates Ten Years, Looks to Next Ten - WUWF - April 25th, 2017
- Scientists want to help you recover heart attack with a 3d printed patch - Industry Leaders Magazine - April 25th, 2017
- Bengals set to hold onto McCarron for at least 1 more year - WTOP - April 25th, 2017
- Mending broken hearts - The Sydney Morning Herald - April 22nd, 2017
- 3D-printed Patch Can Help Mend a 'Broken' Heart | Technology ... - Technology Networks - April 22nd, 2017
- UAB performs Alabama's first transplant where cadaver liver is 'kept ... - Medical Xpress - April 22nd, 2017
- Heart-healing patch has got the beat - New Atlas - April 20th, 2017
- 3D-printed Patch Can Help Mend a 'Broken' Heart - Technology Networks - April 19th, 2017
- 3D-Printed Patch Can Help Mend a 'Broken' Heart | Lab Manager - Lab Manager | News (press release) (blog) - April 18th, 2017
- 3D-printed patch can help mend a broken heart - UMN News - April 14th, 2017
- Bart Starr returns to Tijuana for stem cells - USA Today - April 10th, 2017
- Pioneering Investigators in Experimental Heart Stem Cell and ... - Newswise (press release) - April 9th, 2017
- The mystique of the invisible: Understanding mental illness - Glens Falls Post-Star - March 27th, 2017
- The Equities Research Analysts' Updated EPS Estimates for March, 20th (AIMT, AMID, AUPH, AVD, BDREF, BPTH ... - Petro Global News 24 - March 23rd, 2017
- Hettinger, ND gets state-of-art new clinic and vets - AG Week - March 21st, 2017
- Harvard Scientists Call For Better Rules To Guide Research On 'Embryoids' - Alabama Public Radio - March 21st, 2017
- State-of-art new clinic - and vets - The Dickinson Press - March 19th, 2017
- 3 Women Blinded By Unproven Stem Cell Treatments - Alabama Public Radio - March 16th, 2017
- Hot Biotech Stocks Recap: Nektar Therapeutics (NASDAQ:NKTR), Biostage, Inc. (NASDAQ:BSTG) - The Voice Registrar - March 7th, 2017
- Trump's coal council to drill down on advanced technology - Washington Examiner - March 6th, 2017
- Embryo Experiments Reveal Earliest Human Development, But Stir Ethical Debate - Alabama Public Radio - March 3rd, 2017
- Houston Solar Car featured in IMAX film, Smithsonian - Northeast Mississippi Daily Journal - February 24th, 2017
- News Scan for Feb 20, 2017 - CIDRAP - February 21st, 2017
- On Second Attempt, SpaceX Launches Rocket At NASA's Historic Pad - Alabama Public Radio - February 20th, 2017
- A Liftoff Deferred: SpaceX Mission From NASA's Historic Launch Pad Delayed - Alabama Public Radio - February 19th, 2017
- ECO VIEWS: Advertising is not just for humans - Tuscaloosa News - February 13th, 2017
- ECOViEWS: Advertising is not just for humans - Aiken Standard - February 11th, 2017
- Unsung: Jewel Plummer Cobb - Undark Magazine - February 8th, 2017
- Bart Starr prepares to watch Super Bowl from home as health keeps improving - USA TODAY - February 7th, 2017
- Romero '87 Sees ACLU Donations Soar, Munson *79 to Lead RIT, and More - Princeton Alumni Weekly - February 7th, 2017
- Meet the Team - The University of Alabama at Birmingham - January 26th, 2017
- Tallasee Dog Undergoes Stem Cell Procedure - Alabama News - December 30th, 2016
- Dermal fibroblast - Wikipedia - November 27th, 2016
- Stem Cell Hair Growth Huntsville | Steve Latham Hair ... - September 12th, 2016
- Adult Stem Cell Success - Children of God for Life - April 18th, 2015
- Can cancer vaccines prolong survival? - April 7th, 2015
- Human embryonic stem cells clinical trials - Wikipedia ... - February 19th, 2015
- Christian singer Carman shares testimony of cancer victory - February 2nd, 2015
- Urban Dictionary: stem cell - January 21st, 2015
- Huntsville blood bank to preserve umbilical cord tissues - November 25th, 2014
- CGS : 60 Minutes Exposes Stem Cell Scams Again - November 22nd, 2014
- What Are Stem Cells? (with pictures) - wiseGEEK - November 16th, 2014
- alabama StemCells Therapy StemCells Therapy - October 24th, 2014
- Life Issues Institute - Successes of Adult Stem Cell ... - October 16th, 2014
- A heartbeat away? Hybrid 'patch' could replace transplants - October 1st, 2014
- Huntsville AL Resources - Stem Cells: Get Facts on Uses ... - September 29th, 2014